5-141152828-G-T

Variant names:

• chr5-141152828-G-T
• rs17629216
• NM_018939.4:c.*186G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018939.4(PCDHB6):​c.*186G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000325 in 307,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: PCDHB6 NM_018939.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 0 publications found

Genes affected

PCDHB6 (HGNC:8691): (protocadherin beta 6) This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. Unlike the alpha and gamma clusters, the transcripts from these genes do not share common 3' exons. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell neural connections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

PCDHB@ (HGNC:8679):

ENSG00000280029 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018939.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDHB6	NM_018939.4	MANE Select	c.*186G>T		3_prime_UTR	Exon 1 of 1	NP_061762.2	Q9Y5E3
	PCDHB6	NM_001303145.2		c.*186G>T		3_prime_UTR	Exon 2 of 2	NP_001290074.1	A0A096LNH7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDHB6	ENST00000231136.4	TSL:6 MANE Select	c.*186G>T		3_prime_UTR	Exon 1 of 1	ENSP00000231136.1	Q9Y5E3
	PCDHB6	ENST00000622991.1	TSL:2	c.*186G>T		3_prime_UTR	Exon 2 of 2	ENSP00000485034.1	A0A096LNH7
	ENSG00000280029	ENST00000624192.1	TSL:5	n.73-15645C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000325 AC: 1 AN: 307230 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 154680

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 8000

American (AMR) AF: 0.00 AC: 0 AN: 9122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9206

East Asian (EAS) AF: 0.00 AC: 0 AN: 22100

South Asian (SAS) AF: 0.00 AC: 0 AN: 5170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1346

European-Non Finnish (NFE) AF: 0.00000499 AC: 1 AN: 200594

Other (OTH) AF: 0.00 AC: 0 AN: 17766

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		-0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17629216; hg19: chr5-140532409;